Content-targeted ads are served with e-mail. A unique content identifier (“CUID”) is included in the content. A client device passes the CUID to an ad server in a an ad request. The ad server uses the CUID to identify previously registered content for determining content-relevant ads. Current information may be used when choosing and/or ordering ads. Thus, ads can be chosen and generated when the user “opens” the e-mail. An ad image may display ads in the document. Ad impression information may be encoded in a unique identifier, returned along with the ad image. The ad image and unique identifier may be provided to a client device. This unique identifier and an image map click position may be returned to the ad server upon ad selection. The ad server may use the returned information to determine the selected ad.